Examining the Effects of Immulina to Increase Immune Resilience against Influenza Virus Infections

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PROJECT 2: ABSTRACT/SUMMARY The proposed University of Mississippi (UM) Botanical Dietary Supplements Research Center (BDSRC) is focused on filling in knowledge gaps related to the potential for the Spirulina-based product, ImmulinaTM, to promote resilience against and/or recovery from influenza and, by extension, other respiratory viral infections. During the 2017-18 reporting year in the U.S. alone, influenza resulted in 959,000 patient hospitalizations and 79,400 deaths. The UM BDSRC will be composed of an Administration Core, a Botanical Core, and two research projects. Project 2, Evaluation of ImmulinaTM Oral Supplement for Host Resistance to Influenza Virus Infection, will be directed by Gailen Marshall, MD, PhD, Professor and Executive Director of the Mississippi Clinical Research and Trials Center at UM Medical Center. Working closely with him will be Khalid Ashfaq, PhD, DVM, DTVM. Project 2 is designed to include studies utilizing both mouse models (Years 1-2) and biomarker-based human models (Years 3-5) aimed at establishing the impact of ImmulinaTM supplementation on increasing host resilience against the pathogenic effects of influenza virus infection. It will investigate the following hypothesis: ImmulinaTM given in its optimal oral form will alter the host antiviral immune response, manifested by increases in NK cell numbers and/or activity, anti-flu H and N antibody titers, and CD8+ cytotoxic T lymphocytes (CTL) against flu-infected cells. To investigate our hypothesis, we will achieve the following specific aims: 1. Evaluate oral administration of ImmulinaTM in three non-lethal mouse models of resilience against influenza A virus infection (prophylaxis, prodrome and recovery) to determine the most effective utility of ImmulinaTM for enhancing host immunity to improve antiviral resilience; 2. Confirm that activation of the TLR2 signaling pathway by Braun-type lipoproteins is a primary causal mechanism through which ImmulinaTM enhances host immunity against antiviral infection; 3. Determine the optimal form and dosage of the ImmulinaTM-based supplement in the human model that will maximize effects on increasing NK cell numbers and/or activity, increased supporting cytokines (IL-15, IL- 2, IGNg), influenza-specific antibody titers and CTL numbers; 4. Establish the timeline for optimal NK, cytokine, antibody and CTL responses in terms of both initial changes and maximal changes and duration of the change once the ImmulinaTM is discontinued in normal and immune compromised (elderly) human research participants; and 5. Examine the effects of routine influenzas vaccine given before, during, or after ImmulinaTM use to investigate influenza antigen-specific immune responses in individuals receiving ImmulinaTM supplement vs placebo.